Cutting Salt Restores Vessel Health

by John Gever John Gever Senior Editor, MedPage Today
November 09, 2012

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Patients with moderate hypertension who went on a sodium-restricted diet for 4 weeks showed significant improvements in markers of vascular endothelial function in a small trial.

Note that in an accompanying editorial, two Australian researchers agreed that the study demonstrated that salt reduction was beneficial, but questioned whether the effect was really independent of blood pressure.

Patients with moderate hypertension who went on a sodium-restricted diet for 4 weeks showed significant improvements in markers of vascular endothelial function in a small trial, researchers said.

In a randomized, crossover study of 17 middle-age and older volunteers, endothelial dysfunction seen when their diet contained roughly 3,600 mg/day of sodium was reversed when their intake was closer to 1,200 mg/day, according to Douglas Seals, PhD, of the University of Colorado, in Boulder, and colleagues.

The findings "support the hypothesis that dietary sodium restriction to a level consistent with the Dietary Approaches to Stop Hypertension (DASH) diet improves both conduit artery (macrovascular) and resistance vessel (microvascular) endothelial function in middle-age/older men and women with elevated systolic blood pressure," the researchers wrote online in the Journal of the American College of Cardiology.

They indicated that the effect appears to be mediated by increasing the bioavailability of nitric oxide and tetrahydrobiopterin and by reducing oxidative stress.

In an accompanying editorial, two Australian researchers agreed that the study demonstrated that salt reduction was beneficial, but questioned whether the effect was really independent of blood pressure.

David S. Celermajer, DSc, and Bruce Neal, PhD, both of Royal Prince Alfred Hospital in Sydney, criticized the study authors' statistical methods for controlling for participants' blood pressure.

That aside, though, they argued that the bigger issue now is how to cut average daily sodium intake by 50% or more in large numbers of people.

Celermajer and Neal wrote that the DASH diet "has proven achievable in research studies, but widespread implementation would require action by many stakeholders, including legislators, food companies, and retailers, as well as by consumers."

In the study, Seals and colleagues had the 17 participants, mean age 62 (SD 7) eat the DASH diet for 10 weeks. The diet has a target sodium content of 1,200 mg/day, but because participants were able to stray from it somewhat, their actual daily dietary intake was estimated from food diaries during the study to be about 1,340 mg.

Participants were also randomized to take slow-release salt pills daily -- totaling 2,300 mg of sodium, intended to bring total daily intake to 3,600 mg, close to the actual U.S. adult average -- or matching placebo pills for 4 weeks. After a 2-week washout, participants were switched to the other pill type.

Mean urinary sodium excretion while on the DASH diet without salt supplement was less than half that seen when participants were taking the salt tablets (70 mmol/day versus 153 mmol/day), whereas mean potassium excretion was unchanged. At baseline, mean sodium excretion was 150 mmol/day, indicating that the diet intervention reduced sodium intake substantially.

Other cardiovascular risk markers such as LDL and HDL cholesterol, triglycerides, fasting plasma glucose, and physical activity levels did not differ significantly between the two study conditions.

But in addition to systolic pressure, the low-sodium condition was associated with dramatic increases in flow-mediated dilation in the brachial artery (mean change of 0.23 mm versus 0.15 mm with "normal" sodium intake, P<0.001).

Also, the area under the curve for the percentage change in forearm blood flow in response to acetylcholine challenge compared with saline was greater under the low-sodium condition (mean 1,768 versus 1,213 for "normal" sodium, P<0.05).

Seals and colleagues found a similar difference in the area under the curve for the percentage change in forearm vascular conductance (mean 1,811 versus 1,220, P<0.05).

These differences were abolished when participants were treated with a short-acting inhibitor of nitric oxide synthesis, "indicating increased nitric oxide bioavailability during dietary sodium restriction," the researchers wrote.

And, flow-mediated dilation improved in the "normal" sodium condition, but not during sodium restriction, when participants were given ascorbic acid or oral tetrahydrobiopterin, both of which act to reduce oxidative stress.

Seals and colleagues said these effects were independent of changes in systolic blood pressure associated with the sodium restriction.

But the editorialists questioned that conclusion.

"The methodology employed [in the study] was not a good test [of blood pressure-independent effects of sodium reduction]," Celermajer and Neal wrote.

"Including individuals' blood pressure measurements in statistical models is a poor means of controlling for the effects of change in blood pressure because of the enormous moment-to-moment within-individual variability of blood pressure levels," they argued.

"This means that little of the effect of blood pressure is controlled for when models are fitted in this way, with alternate methods that use grouped data being required to properly explore the blood pressure-dependent versus blood pressure-independent effects of interventions."

For their part, Seals and colleagues acknowledged that the study was limited by the small sample size, although they contended that, thanks to the crossover design, the study was adequately powered for the comparisons made.

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